Establishing the phenotypic basis of adherent-invasiveEscherichia coli(AIEC) pathogenicity in intestinal inflammation

AbstractBackground & AimsAdherent-invasiveEscherichia coli(AIEC) are enriched in ileal Crohn’s disease patients and implicated in disease etiology. However, AIEC pathogenesis is poorly understood, and it is unclear if the expansion of these organisms contributes to inflammatory bowel disease (IBD). Questions also remain as to what extent the variousin vitrophenotypes used to classify AIEC are pathologically relevant.MethodsWe utilized a combination ofin vitrophenotyping and a murine model of intestinal inflammation to systematically relate AIEC phenotypes to pathogenicity for 30 mucosa-associated human-derivedE. colistrains.In vitroassays used included survival/replication in and TNF-α production by J774 macrophages as well as invasion/replication in Caco2 intestinal epithelial cells.ResultsAIEC do not form a phenotypic group that is clearly separated from non-AIEC. However,E. colistrains displayingin vitroAIEC phenotypes caused, on average, more severe intestinal inflammation. Survival/replication of strains in J774 and Caco2 cells were positively correlated with diseasein vivo, while adherence to Caco2 cells and TNF-α production by J774 cells were not. Importantly, co-colonization with adherent non-AIEC strains ameliorated AIEC-mediated disease.ConclusionOur findings do not support the existence of an AIEC pathovar that can be clearly separated from commensalE. coli. However, intracellular survival/replication phenotypes do contribute to murine intestinal inflammation, suggesting that the AIEC overgrowth observed in human IBD makes a causal contribution to disease. The ability to differentiate pathologically-relevant AIEC phenotypes from those that are not provides an important foundation for developing strategies to predict, diagnose and treat human IBD through characterizing and modulating patientE. colipopulations.